Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034,1 Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Campus Universidad Autonoma, 28049 Madrid, Spain,2 Department of Biological Sciences, Faculty of Natural Sciences, University of Ngaoundéré, Ngaoundéré, Cameroon3
Received 6 October 2004/ Returned for modification 15 December 2004/ Accepted 30 March 2005
This study reports the efficacy of a heterologous prime-boost vaccination using DNA and vaccinia viruses (Western Reserve [WR] virus and modified [attenuated] vaccinia virus Ankara [MVA]) expressing the LACK antigen (Leishmania homologue of receptors for activated C kinase) and an intradermal murine infection model employing Leishmania infantum. At 1 month postinfection, vaccinated mice showed high levels of protection in the draining lymph node (240-fold reduction in parasite burden) coupled with significant levels of gamma interferon (20 to 200 ng/ml) and tumor necrosis factor alpha/lymphotoxin (8 to 134 pg/ml). Significant but lower levels of protection (6- to 30-fold) were observed in the spleen and liver. Comparable levels of protection were found for mice boosted with either LACK-WR or LACK-MVA, supporting the use of an attenuated vaccinia virus-based vaccine against human visceral leishmaniasis.
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